tbuckley/cabot-search huggingface dataset:
Next generation sequencing (NGS) testing for cancer patients at a safety NET hospital.
Authors: Rizvan Azimzade, Maria Louise Avenido, Kevin B. Knopf, An Uche
Journal: Journal of Clinical Oncology (2023)

e18563 Background: Next Generation Sequencing (NGS) testing is gradually becoming an essential aspect of cancer care. However, numerous studies have shown that non-White patients are under-represented in both precision oncology clinical trials and molecular testing. Highland General Hospital (HGH) is a community safety-net hospital in Oakland, California serving primarily Black, Hispanic and Asian patients. In an effort to increase health equity, in August 2020 we began to offer NGS testing with Tempus Labs, Inc. for our cancer patients. The purpose of this study is to document this experience and highlight the genomic profile of our patient population. Methods: This is a retrospective chart review study. Patients were included if their tumor biopsy was sent for NGS testing from August 2020 to December 2022. A total of 165 patients had their samples sent for NGS, of which 148 were included in this study and 17 were excluded due to lack of sufficient tissue. Patient demographic data and predictive biomarkers were collected. For the purposes of this study, we defined predictive biomarkers as those that predict likelihood of response or lack of response to therapy as recommended by National Comprehensive Cancer Network guidelines. Results: The racial distribution of our patient sample is shown in the table below. Consistent with the patient population of HGH, our sample included mostly Black (32.4%), Hispanic (26.4%), and Asian (21.6%) patients. Non-Small Cell Lung Cancer (NSCLC) and colorectal cancer (CRC) were the two most common malignancies sequenced at 34.5% and 25.7%, respectively. For NSCLC patients, 54.9% had predictive biomarkers, with EGFR and KRAS being the most common driver mutations. For CRC patients, 60.5% had predictive biomarkers, with 73.9% of those being NRAS/KRAS and 13.0% being high tumor mutational burden. Full results to be presented. Conclusions: Based on our experience, it is feasible and informative to provide NGS testing for patients at safety-net hospitals. NGS testing allows for the most appropriate treatment selection for each patient, which can translate into better outcomes. Moreover, due to the unique demographics of patients from these hospitals, NGS tests can provide valuable information about the tumor genomic profiles of these underrepresented patients. This data can help improve drug development research and close the health equity gap. [Table: see text]
Neoadjuvant versus adjuvant therapy in patients with stage III or IV resectable melanoma: A systematic review and meta-analysis.
Authors: Thiago Madeira, Maysa Vilbert, Jonathan N Priantti, Francisco Cezar A Moraes, Erica C. Koch Hein, Mauricio Fernando Ribeiro, Ludimila Cavalcante, David H. Lawson
Journal: Journal of Clinical Oncology (2023)

e21542 Background: Neoadjuvant therapy (NAT) has emerged as a promising strategy to treat resectable melanoma patients by generating a robust immune response and longer immunologic memory. We performed a systematic review and meta-analysis evaluating the survival benefit of NAT compared to standard adjuvant therapy (AT) for melanoma patients. Methods: We searched for randomized clinical trials (RCT) comparing NAT versus AT in resectable stages IIIB/C or IV melanoma patients on PubMed, Scopus, and Cochrane Library databases. We assessed event-free survival (EFS), distant metastasis-free survival (DMFS), overall survival (OS), and safety. Studies included were limited to RCTs with an adjuvant control arm and reporting at least one of the outcomes of interest. Heterogeneity was examined with the I 2 statistics, and the random effects model was fitted. Results: Four RCTs met inclusion criteria for a total of 504 patients. Most patients had stage IIIB/C (79.1%), and received NAT with immunotherapy (66%), target therapy (4.2%) and talimogene laherparepvec (TVEC) (29.8%). In the pooled analysis of 2-year follow-up: 71.3% of patients in the NAT arm and 53.2% in AT arm were event-free [Risk Ratio (RR): 0.57 95%Cl 0.39-0.83 p=0.003]. Albeit the difference in therapies, NAT decreased by 44% the risk of death compared to AT, with 89.4% and 81.2% of patients alive at two years, respectively (RR 0.56 95%Cl 0.36-0.87 p=0.01). DMFS was reported in three studies (n=191). Patients on NAT had numerically higher DMFS rate (44%) compared to AT (28.6%) (p=0.23). Two studies (n=170) have published 5-year follow-up results: OS rate has remained statistically significant, favoring NAT (RR 0.58 95%Cl 0.34-0.97 p=0.04). Significant differences were not observed in EFS (p=0.06) and DMFS (p=0.08). Adverse events were similar in both groups, and there were no treatment-related deaths. In these studies, there were no significant delays in surgery due to toxicity or unexpected perioperative complications. Combined immunotherapy caused the highest incidence of grade 3/4 toxicity (90%) among the therapies. Conclusions: This systematic review and meta-analysis indicate a significant survival benefit from NAT for stages IIIB/C and resectable stage IV melanoma. NAT induces better anti-tumor activity, leading to improved EFS and OS compared to AT, with similar safety profile. Phase 3 clinical trials with longer follow-up are warranted. [Table: see text]
One way to provide effective healthcare services for patients with advanced cancer to improve their quality of life and survival: Prediction modeling using machine learning techniques and causal relationship between self-management strategy, health-related quality of life, and survival.
Authors: Juyoun Jung, Kyung Hae Jung, Su-Jin Koh, Young Ho Yun
Journal: Journal of Clinical Oncology (2023)

e24005 Background: In healthcare services, self-management strategies can play a crucial role in enhancing the health-related quality of life (HRQoL) or survival of cancer patients, regardless of their stage or treatment plan. However, there needs to be more research addressing the relationship between the strategies, HRQoL, and survival. To address this gap, we investigated the relationship between the strategies, HRQoL, and survival using machine learning techniques (MLT) and path analysis with structural equation modeling (SEM). Methods: This study was a secondary analysis of a randomized controlled trial (RCT) to provide early palliative care to individuals with advanced cancer (ClinicalTrials.gov, ID NCT03181854). We employed dimensional multiple Cox proportional hazard regression analyses to identify the crucial predictors of 1-year survival. By integrating the critical predictors extracted from the Cox regression models, we established a final survival prediction model using the eXtreme Gradient Boost (XGBoost) and the BorutaSHAP in MLT. Furthermore, we used path analysis to investigate the causal relationship between the strategies, HRQoL, and survival. Results: The univariate dimensional Cox models indicated that factors such as worse ECOG performance status (hazard ratio (HR) = 2.18), living alone (HR = 1.74), male (HR = 1.65), low global QoL (HR = 1.81), high dyspnea (HR = 2.30), high pain (HR = 1.75), high appetite loss (HR = 1.94), high constipation (HR = 2.11), high depression (HR = 2.79) at baseline, and no significant positive changes in emotional functioning (HR = 1.88) negatively impacted survival. The final XGBoost model for survival prediction using repeated K-fold methods (K = 5, repeats = 20, area under the receiver operating characteristic curve (AUROC) = 0.76, area under the precision-recall curve (AUPRC) = 0.87) and bootstrapping (n = 300, AUROC = 0.81, AUPRC = 0.91) showed high survival prediction performance. Additionally, the path analysis revealed a causal relationship between self-management strategies, HRQoL, and survival in patients with advanced cancer ( p-value = 0.005). HRQoL was found to have a complete mediating relationship between the strategies and survival. Self-management strategies did not directly correlate with survival but showed an impact on survival through HRQoL. Conclusions: To the best of our knowledge, this is the first study to uncover the connection between self-management strategies, HRQoL, and survival in patients with advanced cancer using MLT and path analysis. These findings have the potential to deepen our understanding of self-management strategies and aid healthcare providers in providing improved cancer care for patients with advanced cancer. Clinical trial information: NCT03181854 .
Safety and clinical activity of TTI-621 in combination with doxorubicin in patients with unresectable or metastatic high-grade leiomyosarcoma: Results from the low-dose expansion cohort.
Authors: Sujana Movva, Mihaela Druta, Lara E. Davis, Varun Monga, Mohammed M. Milhem, Howard Harry Bailey, Rashmi Chugh, Ingmar Bruns, Victoria E Allgood, Sant P. Chawla
Journal: Journal of Clinical Oncology (2023)

11508 Background: TTI-621 is a recombinant fusion protein combining the Fc region of human IgG1 with a fragment of human SIRPα, designed as a decoy receptor for CD47 on tumor cells to interrupt CD47-SIRPα signaling and promote macrophage-mediated phagocytosis of tumor cells as well as activation of NK cells. Preclinical studies suggest TTI-621 may enhance the response to doxorubicin in macrophage-rich tumors that express CD47, such as leiomyosarcoma (LMS). A phase 1/2 dose escalation study with high- and low-dose expansion cohorts evaluating TTI-621 + doxorubicin in patients (pts) with advanced LMS is ongoing (NCT04996004); results from the low-dose expansion cohort are presented. Methods: This open-label study enrolled anthracycline-naïve pts aged ≥18 y with evaluable unresectable or metastatic high-grade LMS and ≤1 prior line of therapy for advanced disease. Pts in the low-dose expansion cohort received TTI-621 0.2 mg/kg on Days 1 and 8 in combination with doxorubicin 75 mg/m 2 on Day 1 of 21-day cycles for a maximum 6 cycles, followed by TTI-621 monotherapy on Days 1 and 15 of 28-day cycles until objective disease progression. Primary objectives for the expansion phase were evaluation of safety and investigation of clinical activity via assessment of overall response and clinical benefit rates as defined by RECIST v1.1 criteria. Results: At data cut-off (Oct 3, 2022), 23 pts were evaluable for safety and 20 for clinical response. In the safety population, 39% had received prior treatment for advanced disease. Two pts (9%) experienced Grade ≥3 AE assessed as related to TTI-621 treatment: pancreatitis (n = 1, 4%) and platelet count decreased (n = 1, 4%). Seven pts (30%) experienced Grade ≥3 AE related to the combination of TTI-621 and doxorubicin, including two pts (9%) each with platelet count decreased and white blood cell count decreased and three pts (13%) with neutrophil count decreased. Grade ≥3 doxorubicin-related AEs were more common (n = 17, 74%); most frequent were neutrophil count decreased (n = 8; 35%), white blood cell count decreased (n = 7; 30%), and neutropenia (n = 6; 26%). One pt experienced an infusion-related reaction (Grade 1 chills) assessed as related to TTI-621. No pts attained complete response, but one pt had a complete resolution of all target lesions. Five pts (25%) attained partial response for an overall response rate of 25%; 11 pts (55%) attained stable disease for a disease control rate of 80%. Conclusions: Addition of TTI-621 to doxorubicin showed promising clinical activity and a favorable safety profile among pts with advanced LMS, including those with prolonged exposure to TTI-621 ( &gt; 360 d). Clinical trial information: NCT04996004 .
Advancing digital innovation to improve equity and reduce financial toxicity in cancer treatment.
Authors: Sarah M Sheehan, Smit Patel, Corinne R Leach, Jennifer C Goldsack, Edmondo J Robinson
Journal: Journal of Clinical Oncology (2023)

e18644 Background: The global burden of cancer is set to increase by more than 60% (to 29.4 million cases) by 2040 . Certain subgroups of patients experience avoidable disparities in access to specialized cancer treatment and discrepancies in clinical outcomes following treatment. The risk of financial toxicity following a cancer diagnosis is also not equally distributed . These disparities in cancer disease burden, treatment, and the risk of financial toxicity have the potential to be disintermediated by digital innovation. Methods: The Digital Medicine Society and Moffitt Cancer Center are co-hosting a pre-competitive collaboration to define the value of digital innovation in cancer treatment, address methodological and implementation gaps, and develop best practices for equitable adoption of digital health technologies at scale in precision oncology. We undertook a landscape review to identify and prioritize causes of disparities and financial toxicity and to benchmark the clinical, engineering, and implementation science dimensions relevant to enhanced digital innovation in cancer treatment. We convened and synthesized information from an expert roundtable which focused on challenges preventing the effective implementation of digital solutions as well as the infrastructure, payment, policy, and regulatory changes needed to promote equity and address financial toxicity with digital health tools. Results: We outline the value of digital innovation in cancer treatment and present consensus-based recommendations from workgroup convening about how digital health tools can be implemented to: Reduce costs associated with advanced cancer treatment and ameliorate disparities in cancer burden by equitably supporting early detection and cancer prevention &amp;nbsp; Advance precision oncology, minimize the costs of delays in accessing the right care and ensure that the best outcomes are available to all cancer patients&amp;nbsp; Reduce disparities in access by extending the best specialist expertise and clinical trial opportunities to all cancer patients&amp;nbsp;. Conclusions: Innovative digital approaches have yet to be applied at scale to minimize the burden of financial toxicity to patients with cancer and to reduce healthcare access and outcomes disparities. The delivery of high-quality precision cancer care for all patients depends on our collective ability to increase access to specialized care, harness flows of existing patient data and the power of decentralized clinical trials, and reduce the impact of social determinants of health on patient outcomes. There is substantial opportunity to leverage the results of this landscape review and convening to 1) build impact models that articulate the value of implementing fit-for-purpose digital solutions to promote equity and reduce financial toxicity, and 2) develop implementation toolkits for the equitable and effective deployment of those solutions.
Selinexor (SEL) plus ruxolitinib (RUX) in JAK inhibitor (JAKi) treatment-naïve patients with myelofibrosis: Updated results from XPORT-MF-034.
Authors: Haris Ali, Ashwin Kishtagari, Keri Renee Maher, Sanjay Mohan, Josef T. Prchal, Xulong Wang, Kamal Chamoun, Srinivas Kiran Tantravahi
Journal: Journal of Clinical Oncology (2023)

7063 Background: Myelofibrosis (MF) is a myeloproliferative neoplasm associated with splenomegaly, high symptom burden, and poor prognosis. Activity has been shown with the combination of SEL + the JAKi RUX in preclinical studies. Specific subgroups with lower response rates to RUX monotherapy, such as males vs females (25% vs 59%) and those with a lower (≤15 mg vs 20 mg) RUX starting dose (22-27% vs 43%), highlight unmet need in specific groups (grps). Methods: XPORT-MF-034 is a Phase 1/2, open-label study evaluating safety and efficacy of SEL at 40 mg and 60 mg once-weekly plus RUX per standard of care in 28-day cycles. Assessments included safety, spleen/symptom response, survival, and hemoglobin levels. The primary analysis population included those who had baseline assessment and were treated to at least Week 24 (W24) or discontinued before W24. Two pts with baseline total symptom score (TSS) = 0 were excluded from analysis of TSS reduction of ≥50% (TSS50). Results: As of Dec 21, 2022, 10 participants received 40 mg and 14 participants received 60 mg SEL; 22 of the 24 pts enrolled had reached at least W24 and were included in the efficacy analysis. The median duration of treatment was 28 wks overall, 33 wks for 60 mg and 22.5 wks for 40 mg grps. Most common adverse events (AEs) by dose (60/40 mg) were nausea (79%/70%; majority grade 1-2), anemia (79%/50%), and fatigue (57%/60%). Most common Grade ≥3 AEs were anemia (50%/40%), thrombocytopenia (29%/10%), and neutropenia (7%/20%). AEs were reversible with dose modifications. Two patients discontinued treatment due to treatment-related AEs (thrombocytopenia and neuropathy); 3 deaths have occurred in the study, none related to SEL. Overall, 64% (14/22) achieved SVR35 at W24, with 79% [11/14] vs 38% [3/8], in the 60 mg vs 40 mg grp, respectively. The 60 mg grp achieved a deeper median SVR response vs the 40 mg grp at W24 (49% vs 31%). At W24, TSS50 was achieved by 45% (9/20) overall, 58% [7/12] of the 60 mg, and 25% [2/8] of the 40 mg grp. Among 11 pts with baseline hemoglobin &lt; 10 g/dL, median hemoglobin decreased by 0.5 g/dL from baseline to W12 and increased by 0.8 g/dL from baseline to W24. Similar efficacy was observed across all subgrps with 60 mg. Reduction of variant allele frequency from baseline to W24 was &gt; 10% in 50% (4/8) and &gt; 20% in 25% (2/8) of evaluable pts for 60 mg grp. Conclusions: Encouraging activity with 60mg SEL + RUX combination were observed in TSS50, SVR and hemoglobin levels overall, as well as in key subgroups including males, in pts started on low dose RUX (≤15 mg), and pts with larger baselines spleen size. Updated data will be available for presentation. Clinical trial information: NCT04562389 . [Table: see text]
Analysis of the efficacy and safety of PD-1/PD-L1 inhibitors–based treatment in myxofibrosarcoma: A single-institution retrospective analysis.
Authors: Chenlu Zhang, Yuhong Zhou, Rongyuan Zhuang, Xi Guo, Yang You, Zhiming Wang
Journal: Journal of Clinical Oncology (2023)

e23531 Background: Myxofibrosarcoma (MFS) is a rare subtype of soft tissue sarcoma (STS), accounting for about 5% of STS. At present, the treatment of advanced or metastatic MFS is limited and the prognosis is poor. PD-1/PD-L1 inhibitors have shown efficacy in some subtypes of STS, but there is no real-world research data of MFS. This study retrospectively analyzed the efficacy and safety of PD-1/PD-L1 inhibitors-based treatment for MFS patients in Department of Oncology, Zhongshan Hospital, Fudan University. Methods: Advanced or metastatic MFS patients who underwent PD-1/PD-L1 inhibitors-based treatment were collected. The primary end point of this study was progress-free survival (PFS), and the secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. RECIST 1.1 and CTCAE 5.0 were used to evaluate the efficacy and safety. Results: From January 1, 2018 to January 5, 2023, a total of 11 patients were included in the study. The median age was 57 years (27-74 years); 7 males and 4 females; 4 in extremities, 3 in retroperitoneum, each of 1 in pelvic cavity, mediastinum, trunk and head and neck. 3 cases were primarily unresectable or metastatic, and 8 cases were postoperative recurrence or metastasis. Treatment included: 1 case (1/11) with PD-1/PD-L1 inhibitors and chemotherapy, 2 cases (2/11) with PD-1/PD-L1 inhibitors and anti-angiogenesis therapy, and 8 cases (8/11) with PD-1/PD-L1 inhibitors combined with chemotherapy and anti-angiogenesis therapy. 3 patients were administrated with radiotherapy to enhance local control. Chemotherapy drugs included gemcitabine, nab-pacilitaxel, epirubicin/pegylated liposomal doxorubicin, dacarbazine, and eribulin. Anti-angiogenesis drugs included anlotinib and regorafenib. 5 cases were treated in first line, and 6 cases were in second line or above. The median baseline length of target lesion was 12.4 cm (1.7-23.9 cm). Four patients had distant metastasis, including lung, bone, pleura and lymph node. The median follow-up time was 17.6 months. The median PFS was 12.2 months (95% CI: 9-NE), and the median OS was 19.1 months (95% CI: 14.3-NE). The ORR is 27% (3/11) and the DCR is 91% (10/11). The ≥grade 3 adverse events (AEs) were neutropenia (36.4%), fatigue (18.2%) and hand-foot syndrome (9.1%). The most common AEs of grade 1-2 were of neutrophil (45.5%), hypothyrosis (27.3%), nausea (27.3%), numbness (18.2%), fatigue (9.1%), anemia (9.1%), hepatic impairment (9.1%), and arrhythmia (9.1%). No treatment-related death happened. Conclusions: This is the first retrospective study revealed that the PD-1/PD-L1 inhibitors-based treatment had good efficacy and tolerable toxicity in Chinese advanced or metastatic MFS patients. Further prospective clinical trials and biomarker research on forecasting the efficacy of immune checkpoint inhibitors of MFS are warranted.
Role of nivolumab maintenance therapy in advanced melanoma patients following severe immune-related adverse events from combination nivolumab and ipilimumab.
Authors: Anna Maloney, Anita Giobbie-Hurder, Miklos C. Fogarasi, Patrick Alexander Ott, F. Stephen Hodi, Tamara A. Sussman, Ann W. Silk, Rizwan Haq, David Liu, Megan Leigh Insco, Elizabeth Iannotti Buchbinder
Journal: Journal of Clinical Oncology (2023)

9520 Background: The combination of ipilimumab (ipi), and nivolumab (nivo) has been shown to be a highly effective treatment for metastatic melanoma. However, immune-related adverse events (irAEs) are common with this treatment, leading to treatment interruption and the use of immunosuppressive agents. There are no data on the impact of resuming single agent nivo on survival outcomes following recovery from the irAE and completion of immunosuppressive treatment. Some physicians hold therapy permanently as done on clinical trials and other physicians resume nivo after steroid taper. Methods: In this retrospective analysis, we examined a cohort of patients treated with ipi/nivo who developed irAEs that required treatment interruption and immunosuppressive therapy. The differences in practice patterns among physicians at our institution allowed us to examine the effect of single agent nivo resumption on survival after treatment of irAEs. Multivariate analysis of clinical factors associated with improved survival was performed. Results: We identified 165 patients who were treated with ipi/nivo and developed irAEs requiring treatment interruption and immunosuppressive therapy. To remove any impact of immediate disease progression on the analysis patients who progressed on ipi/nivo prior to or during treatment hold were removed from analysis. Of the remaining 131 patients, 45 resumed single agent maintenance nivo following the resolution of toxicity and completion of steroid taper. When stratified by age and adjusted for sex, M-stage, LDH, duration of therapy, and type of irAE causing the treatment pause, the effect of resumption of nivo upon survival remained highly significant (p = 0.001). Patients who resumed nivo had an 82% reduction in the hazard of death compared with patients who had not yet or never resumed nivo (HR: 0.18, 95% CI: 0.06 to 0.52). Of the patients who resumed nivo, 12 (26%) patients had subsequent irAEs with 5 patients having grade 3 irAEs (only one of whom had a recurrence of the prior ipi/nivo associated toxicity) and no grade 4 or 5 irAEs were noted. Conclusions: The resumption of single agent maintenance nivolumab following a treatment hold for ipi/nivo associated irAE and completion of immunosuppressive therapy increased overall survival compared to discontinuing nivo permanently in patients with metastatic melanoma after stratification for many factors. Toxicity observed post resumption of single agent nivolumab was manageable with no severe irAEs observed. These results suggest that restarting maintenance nivo post irAEs should be studied prospectively.